Lupus Nephritis

Lupus nephritis (LN) is immune complex glomerulonephritis complicating SLE, affecting 40 to 60% of patients, usually within 5 years of diagnosis.

• More frequent and severe in young women and in patients of African, Hispanic and Asian ancestry.
• ISN/RPS classification: Class I (minimal mesangial), II (mesangial proliferative), III (focal, under 50% glomeruli), IV (diffuse, 50% or more), V (membranous), VI (advanced sclerosis). Activity and chronicity indices guide prognosis.
• Pathogenesis: anti-dsDNA and nucleosome immune complexes, complement activation (low C3/C4), interferon signature.
• Class IV carries the highest risk of ESKD (10 to 20% at 10 years).
• Complications: nephrotic syndrome, hypertension, thrombosis (antiphospholipid syndrome), thrombotic microangiopathy, infection, infertility from cyclophosphamide.

• Proteinuria (often nephrotic), haematuria, oedema, hypertension, rising creatinine.
• Active SLE features: rash, arthritis, serositis, cytopenias, fever.
• Subclinical disease may exist with only mild proteinuria.
• RPGN in severe crescentic disease.

• Urinalysis with microscopy (red cell, granular and cellular casts), 24-hour protein or ratio, creatinine and eGFR.
• Serology: ANA, anti-dsDNA, anti-Sm, C3 and C4 (low in active disease), antiphospholipid antibodies, anti-C1q, CBC.
• Renal biopsy for all patients with suspected LN (proteinuria over 0.5 g/day, active sediment, or unexplained eGFR decline): class, activity and chronicity indices, full-house immunofluorescence (IgG, IgA, IgM, C3, C1q).
• Screen infection (hepatitis B/C, HIV, TB) before immunosuppression.

Class III/IV (proliferative)

• Induction (choose one): mycophenolate mofetil 2 to 3 g/day (or mycophenolic acid 1.44 to 2.16 g) with glucocorticoids; or low-dose IV cyclophosphamide (Euro-Lupus 500 mg every 2 weeks for 6 doses) with glucocorticoids; add belimumab 10 mg/kg IV every 4 weeks or voclosporin 23.7 mg twice daily (with mycophenolate), or obinutuzumab 1000 mg, as triple therapy for better renal response.
• Glucocorticoids: methylprednisolone 250 to 500 mg IV daily for 1 to 3 days, then prednisolone 0.3 to 0.5 mg/kg daily tapered to 5 mg or less by 6 months.
• Severe or crescentic disease: IV cyclophosphamide 0.5 to 1 g/m2 monthly for 6 months.
• Maintenance: mycophenolate 1 to 2 g/day or azathioprine 2 mg/kg daily for at least 3 years; withdraw slowly only after sustained remission.
• Refractory: rituximab 1 g on days 1 and 15, obinutuzumab, anifrolumab, CAR T-cell therapy in trials.

Class V: supportive therapy; if nephrotic or mixed disease, mycophenolate with steroids or cyclophosphamide.

Class I/II: hydroxychloroquine and treat extra-renal disease; low-dose prednisolone for proteinuria over 1 g/day.

All patients

• Hydroxychloroquine 200 to 400 mg daily (up to 5 mg/kg), ACE inhibitor or ARB for proteinuria, SGLT2 inhibitor, blood pressure below 130/80 mmHg, statin, vaccinations, Pneumocystis prophylaxis during intensive therapy, bone protection, contraception (avoid mycophenolate, cyclophosphamide, ACE inhibitors in pregnancy).
• Response: proteinuria under 0.5 to 0.7 g/day and stable eGFR at 12 months (complete response by 12 to 24 months).
• Pregnancy only after 6 months of quiescence; switch to azathioprine, add aspirin 75 to 150 mg from 12 weeks.
• Dialysis and transplantation with disease quiescent for 3 to 6 months.